In the last two months, I have explained why the glucagon stimulation test and adrenal venous sampling should not be used any more for the purpose of pheo diagnosis. In this piece, I will go over a good test that has some value in pheo diagnosis; this is the clonidine suppression test.
First of all, why do we need this test? As I have described in previous postings, the results of pheo markers are not black and white. Most people with normal results do not have pheo. The risk of pheo is substantial if the results are 2-3-fold higher than normal. Those are the easier ones to interpret. The results are harder to digest if they are slightly elevated (higher than normal, but less than 2-3-fold elevated). Clonidine suppression test is intended to clarify the meaning of slightly elevated pheo markers.
Clonidine is a medication used for treating hypertension. It works on the brain to decrease the “sympathetic tone”, that is, the intensity of nerve signals to the adrenal medulla. Clonidine suppresses the release of catecholamines and metanephrines from normal adrenal medulla. Pheo is a tumor of the adrenal medulla and it essentially does things on its own. Catecholamines and metanephrines released from a pheo are less suppressed by clonidine than the normal adrenal medulla. Clonidine is thus used to differentiate pheo from normal.
The test is not really standardized and every center has its own protocol and interpretation criteria. The patient has to be off diuretics, tricyclics, and beta blockers for 1-5 days and off all medications for 12 hours. After an overnight fast, the patient goes to the clinic in the morning, and catecholamines and metanephrines are measured at baseline and 3 hours after taking clonidine. The passing results (no pheo) are 50% decrease and/or back to normal.
The major adverse effect of the test is hypotension, which can be severe.
There are a few caveats about the clonidine suppression test. 1) It should never be considered as a “gold standard” for pheo diagnosis. It is just one of the tests that help diagnosing pheo. 2) The results of the clonidine suppression test can be confusing too. Catecholamines and metanephrines may be trending toward different directions. Some markers may be even higher after clonidine. 3) The test is not needed for most patients. Even in the patient who should benefit most from it, I always find that it confirms my clinical suspicion rather than adds new information. 4) It is contra-indicated if the patients can not be off the medications.
My own experience is that the best use of the clonidine suppression test is for comforting patients who are very anxious about their borderline pheo markers and want all possible reassurance that they do not have pheo.
Dr. Pheo
Subscribe to:
Post Comments (Atom)
This comment has been removed by the author.
ReplyDeleteAnother question, could there be any relationship between a delay in a girls period and having one of these tumors? Just wondering as three of the kids who have the SDHB gene mutation also have had delay and trouble with their periods.
ReplyDeletethanks for all of the good info. I have a much better picture after reviewing your blogs and the comments. I have tested positive for the SDHB gene mutation, as well as many of my siblings and some of their children. In addition to the question about the mutation's affect on mensus in girls, could just having the gene mutation cause symptoms of anxiety even though there is no tumor present. Just wondering. I am going to see a doctor May 4th. Thanks for the good doctor referrals. It really helped.
ReplyDeleteI am actually not aware of any relatioship between SDH mutation and delayed start of periods or anxiety (without tumor). My guess is that these two latter conditions are rather common so they may be coincidental with the SDH mutation.
ReplyDeleteDr. Pheo
I'm wondering if I should request this test for my daughter. She is 14 yo and has been diagnosed with malignant hypertension and hypertensive retinopathy. This all came to light 2 weeks ago when she complained of vision loss. A trip to the Opthomologist and then to the ER and a stay in ICU has us now here. To this point the only test result that has revealed anything is her 24 hr urine:
ReplyDeleteNOREPINEPHRINE NORE=>645 UG/24HR ref range 15-80
EPINEPHRINE 4.2 ug/24h ref range 0.5 - 20
DOPAMINE H898 ug/24h ref range 65-400
ALDOSTERONE 4.1 ng/dL ref range <=21
METANEPHRINES TOTAL 4747 ug/24h ref range 113-414
NORMETANEPHRINE 4633 ug/24h ref range 57-286
METANEPHRINE 114 ug/24h ref range 33-185
She had a MBIG scan I-123 and it came back normal. They did full body (top & bottom) and 360 of the torso and 360 of the head and neck.
The doctors are now mentioning a MRA. Her BP is being controlled (it still goes a little high) on Norvasc and Vasotec. The Norvasc seems to have the greatest effect on her BP.
Dear missvonia,
ReplyDeleteI am almost 100% sure that your daughter has pheo. The correct way of finding the pheo is to do abdominal AND pelvic CT or MRI first. If negative, CT or MRI of the neck and chest. MIBG scan has a fair number of false negative results. It is needed but should not be the first imaging study.
I suspect that she has bilateral adrenal pheo or unilateral large pheo in the abdomen.
Dr. Pheo
This comment has been removed by the author.
ReplyDeleteDear kate,
ReplyDeleteFirst of all, please protect your privacy by not giving out your email address and real name. I suggest that you repost your message after deleting your email address and using perhaps first name only. The reasons that I don't give specific advice to any particular reader are many as I described in my earlier articles.
Now back to your questions. To my knowledge, there is at least 1 report of neuroblastoma in a 5-year-old girl with SDHB mutation. She was still alive at age 33 without recurrence. I don’t know if your son’s syrinx is associated with the neuroblastoma. All carriers of SDHB mutation in your family should be followed with lab tests and imaging.
As I only treat adults and late teens, I don't know much about treatment of neuroblastoma in babies. Dr. Sue O'Dorisio at University of Iowa is an international expert on childhood neuroblastoma. You may want to contact her for suggestions.
Best wishes,
Dr. Pheo
Dr. Pheo,
ReplyDeleteThank you for your response. I should have mentioned that they have done an MRI, but the focus was on the head, heart and renal arteries. So the nephrologist decided to order the MIBG scan. Sounds like, in your opinion, I need to insist on a repeat of the MRI or a CT. Which of those would you recommend as a better tool? Also, do you recommend the Clonidine suppression test as well, or do you feel that the 24 hr urine results that I shared are telling enough of a story on their own?
Hello dr. Pheo.
ReplyDeleteI am a medical student from Europe (Romania) and I have a more sophisticated question.
I tend to sweat a lot, even with little emotional stress or heat, and so does my father. Usually this is not a problem, but it is a little bothering me.
The sweating is preceded by bilateral "waves of heat" that raise from abdominal region, kind of precisely where adrenal glands are, towards the face and neck, followed by flushing , sweating and a bit raise of temperature.
Doctors say it is just a form of anxiety or panick attacks. But I am not the anxious type at all. I am a leader everywhere, just that this vasomotor phenomena sometimes bother me.
My understanding of this is that this are discharges of Epinefrine from adrenal medulla.
I do not have Pheo ( as far as my blood tests say ).
Is there a theoretical pathophysiological possibility that I might have an overreactive adrenal gland that discharges too much epinephrine and causes this symptoms ?
My father was also bothered by this symptoms since he was young. Now they decreased as he gets older.
Is a low dose of clonidine helpful in such case ? I don't feel that I am sick, I am just bothered by this hyperhidrosis episodes.
I understand that this issue does not fully fall into some category in the textbook. :)
Sorry if I made some mistakes while writting.
Best regards. Razvan
Thank you
Dear missvonia,
ReplyDeleteMRI is slightly better than CT. Her pheo markers are very high so that she does not need the clonidine suppression test.
Dr. Pheo
Dear Razvan,
ReplyDeleteIt sounds like that your sweating is more of a nuisance than a disease. I suggest that you avoid conditions that would elicit your sweating. The causes of excessive sweating are many. I would not use clonidine just for sweating.
Dr. Pheo
Dear Dr.Pheo ,
ReplyDeleteAvoidance is not the answer for me, because I am very active, involved in many activities and don't want to isolate myself in any way. Avoidance behavior already means textbook "anxiety disorder" and I deeply believe I do not have that.
I ruled out many of the conditions or causes that might cause excessive sweating such as tuberculosis, neoplasms, overactive thyroid , any kind of neurological disorder, heart condition. I am even ready to be realistic and admit it as a personal trait... but...
this episodes are paroxystical not just excessive ( I do not sweat all the time, it just come out of the blue ) , are accompanied by racing heart, elevated BP and sensation of heat all over the body which looks like a massive discharge of epinephrine. Pheo tests are borderline. I mentioned the sweating alone just because the tachycardia and slightly elevated BP don't really bother me, as I am a professional swimmer and this is no big deal for my cardiovascular system at this point.
I still think I have to aproach this in some way, as I am not willing to avoid things that trigger the sweating and the rest because this means changing my life completely.
Sorry to insist on this one. I am not expecting a solution from you. Just trying to see a different opinion.
Thank you.
Dr. Pheo:
ReplyDeleteWhat significance does ultra sounding the thyroid have on pheo/paraganglioma testing?
thank you
kd
Dear kate,
ReplyDeleteThere is no intrinsic value of thyroid ultrasound in management of pheo. In multiple endocrine neoplasia type II, medullary thyroid cancer and or parathyroid adenoma acompany pheo. In those patients, I use blood tests for screening rather than thyroid ultrasound. If the test results are positive, then I do thyroid ultrasound. These tumors, however, are not features of SDH mutations.
Dr. Pheo
Dr. Pheo: I know you do not treat children and that there are Neuroblastoma experts in the country. Could you recommend someone to talk to or share with me about what scans would be done on a young toddler with a history of neuroblastoma with SDHB mutation (new finding)? He is currently doing monthly urine (spot check-i think the hospital that it goes to is UCLA). He had a clean MRI and clean MIBG since his resection. I also believe he is to do monthly ultrasounds for up to 6 months.
ReplyDeleteAny advice would be welcome-
Thank you
Kate
Dear kate,
ReplyDeleteAs I mentioned earlier, Dr. Sue O'Dorisio at University of Iowa is an international expert on childhood neuroblastoma. I suggest that you contact her. Her phone can be obtained from her website.
Dr. Pheo
I have had eight months of burning facial flushing. migb123 showed uptake on anterior images of region of the epigastrium below the left lobe of the liver. Blood pressure normally 140/80,Slightly elevated Metanphrines. Blood normetanphrine slightly elevated, nothing showed up on mri or ct. I am looking for a good surgeon and complete diagnosis of the location of the pheo. I live in el paso,texas. and have had a very hard time finding anyone that specializes in pheo tumors.
ReplyDeleteI am not sure if you do have pheo. Please check my earlier posting on pheo experts. Dr. Jimenez at MD Anderson is an expert on pheo.
ReplyDeleteDr. Pheo
Dr. Pheo:
ReplyDeleteMy best friend is pregnant with very high blood pressure (210/110). A VMA urine test was done. Her results are as follows:
VNA=10.9
total metanephrines was 1.4 mg
normal vma = 6 mg
metanephrone .3-.9 mg
Is this cause for concern?
Thanks in advance-
Kate
Dr. Pheo:
ReplyDeleteMy doctor ordered the Methoxytyramine test for dopamine secreting paragangliomas but apparently Quest Laboratories does not offer the test (or even know what it is). Perhaps he wrote it down wrong....what is the official name for this test and do you know which labs would be able to process it?
Thank you,
Stacey
Dear Kate,
ReplyDeleteThe urine test results are of concern. Pheo in pregnancy is very rare but has serious consequences to the mother and baby. I suggest measuring plasma metanephrines because this test is less affected by the physiological changes during pregnancy. Regardless whether she has pheo, the blood pressure needs to be well controlled.
Dr. Pheo
Dear Stacey,
ReplyDeleteYour doctor wrote the test name correctly. The problem is to find a commercial lab to measure it. My impression was also that Quest might have it but I just checked the Quest website and could not find it. The plasma catecholamines provide some but not as accurate information about dopamine levels. You may ask your doctor where to send the specimen.
Dr. Pheo
Dear Doctor Pheo,
ReplyDeleteMy endo ordered a clonidine suppression test after some abnormal findings. My baseline serum normetanephrines were 309 pg/ml (0-145)and metanephrine was 408 pg/ml (0-62). A ct scan showed a benign adrenal incidentaloma about 1.3 cm but repeat MRI showed none. The clonodine suppression test showed very normal baseline levels of 27 (0-62) for metanephrines and 58 (0-145) for normetanephrines. 3 hours after the clonodine suppression test, my normetanephrines rose to 137 (0-145) and 31 (0-62) for metanephrines. My endo has concluded that my case is odd. Any perspectives? Also, he has ordered the MIBG exam, can progesterone or hydrocortisone or florinef interfere at all with this test? Thanks.
Jill
My endocrinologist is doing a workup to find secondary causes of hypertension, due to a history of emergency level severe paroxysms of hypertension (as far back as 15 years, including one episode of tachycardia, and multiple episodes of coital cephalgia), along with the development of metabolic syndrome, which no one else in the family has.
ReplyDeleteAs a result of dyspnea and chest pain, a nuclear stress test revealed anterior and inferolateral perfusion defects in the heart, suggesting 100% blockage of two arteries, but a catheterization revealed no stenosis, and mild aneurysmal changes to the heart arteries.
I also had several severe episodes of hypotension during a minor surgery a year ago, followed by respiratory arrest that lasted 5 hours. Following the surgery, I developed an acute C-DIFF infection with colonitis and diverticulitis. While in the hospital for that, my blood sugar was slightly elevated.
6 months ago I felt horrible and had my blood sugar checked and it was over 400. My cholesterol, triglycerides, blood pressure - all high, so I'm on meds for it all. Full blown metabolic syndrome.
My urinalysis showed the following abnormal results:
metanephrine 579 mcg (58-203)
normetanepphrine 837 (88-649)
total 1416 (182-739)
VMA 8.4 mg (<= 6)
creatinine 4.78g (0.63 - 2.50)
Having reviewed the literature online, I have discovered that apnea (OSA) may present false positive results, but to what extent, I can't ascertain.
I have OSA (what don't I have at this point? lol), but it's treated, and I'm 100% compliant with treatment. The literature suggests that treatment should correct elevated metanephrines.
So I made an appointment next week to see the sleep specialist with all this information. I'll likely repeat my sleep study, see if there are changes in the condition, and ask for a new CPAP machine. My endocrinologist is redoing the metanephrine tests to confirm the findings ( plasma and 24 hr urine). He also did an MRA to rule out renal artery stenosis.
Years ago when all this started, I had a work-up to rule out autoimmune disease. During that, they found high liver functions (they've been high off and on ever since - high enough to disqualify me ass a plasma donor), high ferritin, and a small hypodense area in one of the lobes of my liver. I went in for a biopsy and was told it had shrunk and there was no need to biopsy. I had a CT scan prior to surgery last year and they found a very small hypodensity in the liver (same place). Interesting, my liver functions dropped to normal shortly after statin treatment - drugs that normally cause an increase in liver functions. They say it's due to my glucose being under control, but I wonder about that, because that was under control before I started the statins, and the tests were abnormal for well over a decade before I developed diabetes.
Anyway - my health has been poor for a very long time. It's tiring, and seeing it get drastically worse is disheartening. I'm young (44), creative, smart, and have very little energy to deal with anything.
Am I right in considering this may simply be the apnea worsening, or do my findings suggest something else may be going on?
Thanks,
John
Dear Jill,
ReplyDeleteThe first plasma metanephrines are quite alarming but the clonidine suppression test results are normal. High dose of hydrocortisone may release metanephrines from an otherwise not-so-obvious pheo. I don't know if progesterone or fludrocortisone does the same. Your doctor should figure out if there were interfering medications you took with the first test. The chance that you have pheo is not high. I will feel more comfortable if repeat testing of plasma metanephrines are normal in 3 months.
Dr. Pheo
Dear John,
ReplyDeleteIn your particular case, the plasma metanephrines are a better test than urine metanephrines. You had a large urine volum which tends to give the impression of elevated urine markers. Based on the current information, I think that you have a low to moderate risk of having pheo. I suggest testing plasma metanephrines. The MR angiogram will also tell if the adrenal glands are normal or not. Sleep apnea does cause elevation of pheo markers but it is a diagnosis of exclusion.
Dr. Pheo
Dear Doctor Pheo,
ReplyDeleteIn my case, my doctor wants to do the MIBG exam to rule out a pheo especially since the first CT picked up a very small adrenal tumor. Would there be any harm in taking this test? Might it help? Why would a ct pick up a tumor and an mri none? You said my clonodine suppression test was normal but my normetanephrines rose to 137 (0-145)from 58. Wikipedia, which may not be reliable, said that if the levels do not suppress to 50% then it is a positive test. My levels rose even though in the normal range. If a pheo is not the cause, how do I treat this to block the unpleasant anxiety? I do not have high blood pressure at all and it actually tends to be on the low side. Thanks for all your insight.
Jill
Thanks for mentioning urine volume. I checked the report and it shows a volume of 2950! I actually did two 24 hour collections; one was for aldosterone, which came out normal. The lab report lists 2950 as the volume for each of these tests.That number clearly represents the combined volume of the speciments, which were collected in 2 separate 4000 mL containers with contents less than 2000 mL in each.
ReplyDeleteI wonder if someone combined the two samples together prior to testing?
I also wonder why I am having to pay for it if they did. Wouldn't ALL the data be wrong?
Dear Jill,
ReplyDeleteThe MIBG scan does not cause physical harm but probably won't add much to determine if you have pheo and may even make things more complicated.
Please read my post in April 2009 for pheo imaging nuances.
If the basal metanephrines are normal, the clonidine test results do not mean much.
Many diseass mimic pheo symptoms. I suggest that you work with your doctors to find out what cause your symptoms and treat them.
Dr. Pheo
Dear John,
ReplyDeleteLab errors are possible but hard to confirm.
Dr. Pheo
Hi Dr Pheo,
ReplyDeleteI am due for a clonidine supression test soon. My HR is between 40 and 50 and not from being fit! Should I be concerned the clonidine dose will lower my HR to unwell levels?!
Many thanks,
Tom
Dear Tom,
ReplyDeleteYou should be concerned. Clonidine can lower your heart rate further. Your doctor and you should weigh the benefits and risks of the test. Alternative approaches are also possible.
Dr. Pheo
Dr. Pheo, do you know anyone at UNM in Albuquerque, NM that might be able to help me? I have been diagnosed with a possible pheo (just need an MRI to confirm). I am really getting the runaround from my HMO run hospital. Any advice you have would be a huge blessing!
ReplyDeleteDear psarahg33,
ReplyDeleteI don't know who is the pheo specialist but a university center should have someone more or less familiar with pheo. I would suggest that you call their endocrine division to see who sees pheo.
Dr. Pheo